CN113185433B - 一种亚硫酸氢钠甲萘醌的制备方法 - Google Patents
一种亚硫酸氢钠甲萘醌的制备方法 Download PDFInfo
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- CN113185433B CN113185433B CN202010038080.5A CN202010038080A CN113185433B CN 113185433 B CN113185433 B CN 113185433B CN 202010038080 A CN202010038080 A CN 202010038080A CN 113185433 B CN113185433 B CN 113185433B
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- sodium
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- MJVAVZPDRWSRRC-UHFFFAOYSA-N Menadione Chemical compound C1=CC=C2C(=O)C(C)=CC(=O)C2=C1 MJVAVZPDRWSRRC-UHFFFAOYSA-N 0.000 title claims abstract description 75
- 229940041603 vitamin k 3 Drugs 0.000 title claims abstract description 31
- 235000012711 vitamin K3 Nutrition 0.000 title claims abstract description 15
- 239000011652 vitamin K3 Substances 0.000 title claims abstract description 15
- 238000002360 preparation method Methods 0.000 title abstract description 19
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 title abstract description 14
- 229910000342 sodium bisulfate Inorganic materials 0.000 title abstract description 14
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims abstract description 48
- 238000006243 chemical reaction Methods 0.000 claims abstract description 42
- SRJCJJKWVSSELL-UHFFFAOYSA-N 2-methylnaphthalen-1-ol Chemical compound C1=CC=CC2=C(O)C(C)=CC=C21 SRJCJJKWVSSELL-UHFFFAOYSA-N 0.000 claims abstract description 29
- GANIBVZSZGNMNB-UHFFFAOYSA-N 2-methyl-1-tetralone Chemical compound C1=CC=C2C(=O)C(C)CCC2=C1 GANIBVZSZGNMNB-UHFFFAOYSA-N 0.000 claims abstract description 26
- 238000000034 method Methods 0.000 claims abstract description 24
- QGLBZNZGBLRJGS-UHFFFAOYSA-N Dihydro-3-methyl-2(3H)-furanone Chemical compound CC1CCOC1=O QGLBZNZGBLRJGS-UHFFFAOYSA-N 0.000 claims abstract description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 47
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 39
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 36
- 238000003756 stirring Methods 0.000 claims description 33
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 claims description 30
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 claims description 30
- 239000002904 solvent Substances 0.000 claims description 28
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 21
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- HYPYXGZDOYTYDR-HAJWAVTHSA-N 2-methyl-3-[(2e,6e,10e,14e)-3,7,11,15,19-pentamethylicosa-2,6,10,14,18-pentaenyl]naphthalene-1,4-dione Chemical compound C1=CC=C2C(=O)C(C/C=C(C)/CC/C=C(C)/CC/C=C(C)/CC/C=C(C)/CCC=C(C)C)=C(C)C(=O)C2=C1 HYPYXGZDOYTYDR-HAJWAVTHSA-N 0.000 claims description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
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- 238000010992 reflux Methods 0.000 claims description 14
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- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 4
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- QIMMUPPBPVKWKM-UHFFFAOYSA-N 2-methylnaphthalene Chemical compound C1=CC=CC2=CC(C)=CC=C21 QIMMUPPBPVKWKM-UHFFFAOYSA-N 0.000 description 12
- 239000003054 catalyst Substances 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 230000035484 reaction time Effects 0.000 description 8
- 239000000243 solution Substances 0.000 description 7
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 7
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- XDPFHGWVCTXHDX-UHFFFAOYSA-M menadione sodium sulfonate Chemical compound [Na+].C1=CC=C2C(=O)C(C)(S([O-])(=O)=O)CC(=O)C2=C1 XDPFHGWVCTXHDX-UHFFFAOYSA-M 0.000 description 6
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Abstract
本发明提供一种亚硫酸氢钠甲萘醌的制备方法,该方法利用α‑甲基‑γ‑丁内酯和苯为原料,经傅克反应制备2‑甲基‑3,4‑二氢‑1(2H)‑萘酮,然后和卤代试剂于羰基邻位进行卤代反应、碱消除制备2‑甲基‑1‑萘酚,2‑甲基‑1‑萘酚经空气氧化得到2‑甲基‑1,4‑萘醌,2‑甲基‑1,4‑萘醌与亚硫酸氢钠经加成反应制备亚硫酸氢钠甲萘醌。本发明方法原料价廉易得,成本低;工艺操作安全简便,工艺废水产生量少,绿色环保;原料及中间产物稳定性高,反应活性和选择性高,反应条件易于实现,副反应少,产品纯度和产率高,利于亚硫酸氢钠甲萘醌的工业化生产。
Description
技术领域
本发明涉及一种亚硫酸氢钠甲萘醌的制备方法,属于有机合成技术领域。
背景技术
亚硫酸氢钠甲萘醌(I),又名维生素K3,英文名为Menadione sodium bisulfite,CAS号为130-37-0,化学名为2-甲基-1,4-萘醌亚硫酸氢钠,分子式为C11H8O2NaHSO3·3H2O,相对分子量330.29,为白色或浅黄色结晶性粉末,无臭或微有特臭,易溶于水,微溶于乙醇、异丙醇和丙酮,不易挥发,易吸潮,遇光分解,无气味,略苦。亚硫酸氢钠甲萘醌是畜禽生命活动不可缺少的营养元素,是饲料添加剂的必要成份。它的主要功能是在动物肝脏内参与凝血酶的合成,有效防治出血性疾病,具有止血、解痉、镇痛及抑制或破坏肿瘤细胞生长的作用,能有效的防治畜禽出血性疾病,促进畜禽生长发育,亚硫酸氢钠甲萘醌还能加速骨骼的矿化作用,参与家禽胚胎形成,保证幼雏存活率。亚硫酸氢钠甲萘醌在与其它药物同用时,可防治球虫病、白痢及霍乱等疾病。除此之外,亚硫酸氢钠甲萘醌还可用于植物生长调节剂、促进剂、除草剂等。亚硫酸氢钠甲萘醌属于小品种维生素,目前60%以上用作饲料添加剂,饲料级全球需求量为5500吨,预计未来5年需求量将以每年4-6%的速度增长,因此该化合物具有广阔的开发和应用前景。
亚硫酸氢钠甲萘醌的结构式如下:
中国专利文献CN105037125A公开了一种亚硫酸氢钠甲萘醌的制备方法,该方法为:将2-甲基萘溶解于烃类溶剂中,加入十二烷基磺酸钠和铬离子氧化液进行氧化反应,反应结束后,反应液经纯化得2-甲基-1,4-萘醌;向2-甲基-1,4-萘醌中加入水和乙醇搅拌溶解后,加入亚硫酸氢钠进行磺化反应,反应结束后,反应液经纯化即得亚硫酸氢钠甲萘醌。以上过程描述为以下合成路线1。
合成路线1
上述合成路线1需采用铬酐氧化体系,产生大量铬盐废水,环保性差;2-甲基萘不易获得,价格高;所涉及的反应选择性差、产率低(总产率最高为75.7%),不适于绿色工业化生产。
中国专利文献CN103833541A公开了一种2-甲基-1,4-萘醌的新合成方法,该方法使用间氯过氧苯甲酸在溶剂冰醋酸中氧化2-甲基萘,反应结束后用氯仿萃取,萃取液经饱和碳酸氢钠、水洗涤后,再用无水硫酸钠干燥,减压蒸馏得到2-甲基-1,4-萘醌,收率31%;所得2-甲基-1,4-萘醌可用于制备亚硫酸氢钠甲萘醌。以上过程描述为以下合成路线2。
合成路线2
上述合成路线2虽然避免铬离子氧化造成的重金属污染,但因所用2-甲基萘和间氯过氧苯甲酸价格高,且收率低,造成成本高,无工业化应用价值。
综上所述,现有技术中,亚硫酸氢钠甲萘醌的制备方法存在反应选择性差、副反应多、产品纯度和收率低、环保性差、成本高等弊端,因此设计一条完整、绿色环保、易于实现、成本低、高反应选择性以及收率和纯度的亚硫酸氢钠甲萘醌的合成路线具有重要意义。
发明内容
针对现有技术的不足,本发明提供一种亚硫酸氢钠甲萘醌的制备方法。本发明方法原料价廉易得,成本低;工艺操作安全简便,工艺废水产生量少,绿色环保;原料及中间产物稳定性高,反应活性和选择性高,反应条件易于实现,副反应少,产品纯度和产率高,利于亚硫酸氢钠甲萘醌的工业化生产。
术语说明:
式Ⅱ化合物:α-甲基-γ-丁内酯;
式Ⅲ化合物:2-甲基-3,4-二氢-1(2H)-萘酮;
式Ⅳ化合物:2-甲基-1-萘酚;
式Ⅴ化合物:2-甲基-1,4-萘醌;
式Ⅰ化合物:2-甲基-1,4-萘醌亚硫酸氢钠,或亚硫酸氢钠甲萘醌。
本说明书中的化合物编号与结构式编号完全一致,具有相同的指代关系,以化合物结构式为依据。
本发明的技术方案如下:
一种亚硫酸氢钠甲萘醌的制备方法,包括步骤:
(1)通过使式Ⅱ化合物和苯经傅克反应制备式Ⅲ化合物;
(2)通过使式Ⅲ化合物和卤代试剂经卤代反应,然后经消除反应制备式Ⅳ化合物;
(3)通过使式Ⅳ化合物氧化制备式Ⅴ化合物;
(4)通过使式Ⅴ化合物和亚硫酸氢钠反应制备亚硫酸氢钠甲萘醌(Ⅰ)。
根据本发明优选的,步骤(1)中,式Ⅱ化合物和苯的傅克反应是于溶剂A中、催化剂的作用下进行的。
优选的,所述溶剂A为二氯甲烷、三氯甲烷、四氯化碳、1,2-二氯乙烷或苯中的一种或两种以上的组合;所述溶剂A和式Ⅱ化合物的质量比为1-20:1;进一步优选的,所述溶剂A和式Ⅱ化合物的质量比为5-12:1。
优选的,所述催化剂为三氯化铝、三氟化硼、氯化锌、四氯化钛或四氯化锡;进一步优选的,所述催化剂为三氯化铝或四氯化钛;所述催化剂和式Ⅱ化合物的摩尔比为(2.0~5.0):1;进一步优选的,所述催化剂和式Ⅱ化合物的摩尔比为(3.0~4.0):1。催化剂用量过多造成浪费、成本提高,催化剂用量过少会导致反应不彻底,非环合副反应产物多。
优选的,所述催化剂如为固体,则于40-60℃下、1-3小时内分批加入至含式Ⅱ化合物的体系中;所述催化剂如为液体,则于40-60℃下、1-3小时内滴加入含式Ⅱ化合物的体系中。
优选的,所述式Ⅱ化合物和苯的摩尔比为1:5-15。
优选的,所述傅克反应温度为40~120℃;进一步优选的,所述傅克反应温度为60~90℃。傅克反应时间为5~20小时;进一步优选的,傅克反应时间为10~16小时。反应温度过高副反应会增多。
根据本发明优选的,步骤(2)中,式Ⅲ化合物和卤代试剂的卤代反应是于溶剂B中进行的。
优选的,所述溶剂B为二氯甲烷、三氯甲烷、四氯化碳、1,2-二氯乙烷、三氯乙烷、环己烷、沸程为60-90℃的石油醚、正己烷或氯苯中的一种或两种以上的组合;所述溶剂B和式Ⅲ化合物的质量比为1-15:1;进一步优选的,所述溶剂B和式Ⅲ化合物的质量比为3-8:1。
优选的,所述卤代试剂为氯气、N-氯代丁二酰亚胺、盐酸-次氯酸钠、盐酸-双氧水、盐酸-氯酸钠、三氯异氰尿酸、溴素、N-溴代丁二酰亚胺或氢溴酸-双氧水;所述盐酸-次氯酸钠、盐酸-双氧水、盐酸-氯酸钠中,盐酸和次氯酸钠、双氧水或氯酸钠的摩尔比为1-1.2:1,所述氢溴酸-双氧水中,氢溴酸和双氧水的摩尔比为1-1.2:1;优选的,所述卤代试剂为氯气、盐酸-双氧水、氢溴酸-双氧水或溴素;所述卤代试剂中起卤代作用的化合物和Ⅲ化合物的摩尔比为(0.95~1.3):1;优选的,所述卤代试剂中起卤代作用的化合物和Ⅲ化合物的摩尔比为(1.0~1.2):1。所述盐酸-次氯酸钠、盐酸-双氧水、盐酸-氯酸钠、氢溴酸-双氧水中,盐酸和氢溴酸为起卤代作用的化合物,剩余组分为氧化剂;且氧化剂是以滴加的方式加入含有起卤代作用的化合物的体系中。
优选的,所述卤代反应温度为20~100℃;进一步优选的,所述卤代反应温度为20~60℃。卤代反应时间为1~10小时;进一步优选的,卤代反应时间为2~8小时。卤代反应温度过高会导致苯环上卤代副反应。
根据本发明优选的,步骤(2)中所述消除反应是于碱存在下进行的。
优选的,所述碱为氢氧化钠、氢氧化钾、氢氧化钙、碳酸钠、碳酸钾、氢氧化锂、三乙胺、氨水、三正丁胺、二异丙基乙胺或吡啶;所述碱和式Ⅲ化合物的摩尔比为(1.0~1.3):1。
优选的,所述消除反应温度为0~100℃;进一步优选的,所述消除反应温度为20~50℃。消除反应时间为1~6小时;进一步优选的,消除反应时间为2~4小时。消除反应温度过高会产生溴自由基导致产生副产物聚合物。
根据本发明优选的,步骤(3)中式Ⅴ化合物的制备包括步骤:于溶剂C中,式Ⅳ化合物被空气氧化制备式Ⅴ化合物。
优选的,所述溶剂C为水、甲醇、乙醇、异丙醇、叔丁醇、乙腈、苯、甲苯或对二甲苯中的一种或两种以上的组合;进一步优选的,所述溶剂C为甲苯、对二甲苯或异丙醇;所述溶剂C和式Ⅳ化合物的质量比为(1-50):1;进一步优选的,所述溶剂C和式Ⅳ化合物的质量比为(3-20):1。
优选的,所述氧化反应温度为20-180℃;进一步优选的,所述氧化反应温度为70-100℃。氧化反应时间为2-8h。
根据本发明优选的,步骤(4)中,式Ⅴ化合物和亚硫酸氢钠的反应是于溶剂D中进行。
优选的,所述溶剂D为甲醇、乙醇、乙腈、正己烷、甲苯、二甲苯、乙酸乙酯、二氯甲烷或氯仿中的一种或两种以上的组合;进一步优选的,所述溶剂D为甲醇、乙醇、乙腈或甲苯;所述溶剂D和式Ⅴ化合物的质量比为(1-20):1;进一步优选的,所述溶剂D和式Ⅴ化合物的质量比为(2-8):1。
优选的,所述亚硫酸氢钠是使用质量浓度为10-30wt%的亚硫酸氢钠水溶液。
优选的,所述亚硫酸氢钠和式Ⅴ化合物的摩尔比为(1-5):1;进一步优选的,所述亚硫酸氢钠和式Ⅴ化合物的摩尔比为(1-1.5):1。
优选的,所述反应温度为0-80℃;进一步优选的,所述反应温度为30-50℃。所述反应时间为1-8小时;进一步优选的,所述反应时间为3-5小时。反应温度过高会导致式Ⅴ化合物的聚合副反应。
根据本发明,本发明的后处理方法可按现有技术;优选的,本发明后处理方法包括步骤:
a、步骤(1)中,式Ⅱ化合物和苯经傅克反应所得反应液冷却至20-25℃,加入质量浓度为30-35wt%的浓盐酸和冰水的混合物中,分层,水层用二氯甲烷萃取,合并有机相,蒸馏回收二氯甲烷和溶剂A,减压蒸馏(115-125℃/1mm汞柱)即得式Ⅲ化合物;
b、步骤(2)中,经消除反应所得反应液冷却至20-25℃,盐酸酸化体系pH至3.0-4.0,分层,水层用溶剂B萃取,合并有机相,蒸馏回收溶剂B,干燥,即得式Ⅳ化合物;
c、步骤(3)中,式Ⅳ化合物氧化所得反应液经活性炭脱色、过滤、滤液经重结晶,然后经过滤、干燥即得式Ⅴ化合物;
d、步骤(4)中,式Ⅴ化合物和亚硫酸氢钠反应所得反应液降温至0℃,结晶1-3小时,过滤,即得亚硫酸氢钠甲萘醌(I)。
本发明的反应过程描述为以下合成路线3:
合成路线3
本发明的技术特点和有益效果:
1、本发明提供了一种新的亚硫酸氢钠甲萘醌的制备方法,该方法利用α-甲基-γ-丁内酯和苯为原料,经傅克反应制备2-甲基-3,4-二氢-1(2H)-萘酮,然后和卤代试剂于羰基邻位进行卤代反应、碱消除制备2-甲基-1-萘酚,2-甲基-1-萘酚经空气氧化得到2-甲基-1,4-萘醌,2-甲基-1,4-萘醌与亚硫酸氢钠经加成反应制备亚硫酸氢钠甲萘醌。
2、本发明路线采用α-甲基-γ-丁内酯为原料,摒弃了传统路线使用的价格较高的2-甲基萘和铬酐氧化步骤,降低了成本的同时,避免了铬盐废水的产生,对环境友好;并提高了反应的选择性,减少了副反应,提高了反应收率。采取傅克反应、卤代-消除、氧化得到2-甲基-1,4-萘醌,此路线反应专一性和选择性高,副反应少,目标产物含量较高。本发明利用2-甲基-3,4-二氢-1(2H)-萘酮的羰基活化作用,和适当量的卤代试剂于羰基邻位进行卤代反应,反应易于进行,并且反应位点专一,无副反应,所得卤代产物不经分离,直接在碱作用下消除卤化盐,得到2-甲基-1-萘酚,所经过程均为高选择性经典反应,易于放大和控制,反应收率高,产品纯度高。2-甲基-1-萘酚关键中间体的获得奠定了该亚硫酸氢钠甲萘醌制备路线的可工业化。最后2-甲基-1,4-萘醌和亚硫酸氢钠进行加成反应得到亚硫酸氢钠甲萘醌(维生素K3),反应选择性高,副反应少,反应条件温和。总之,本发明所涉及的反应活性和选择性高,副反应少,反应原料及中间产物稳定性高,最终目标产物纯度和收率高,总收率可达88.8%。
3、本发明方法不使用2-甲基萘、间氯过氧苯甲酸等价格较高的原料,所用原料价廉易得,成本低;反应条件易于实现,无含铬废水产生,绿色环保;本发明所涉及的原料及中间产物稳定性高,反应选择性高,副反应少,目标产物收率和纯度高,利于亚硫酸氢钠甲萘醌的工业化生产。
具体实施方式
以下结合实施例详细说明了本发明,但本发明不仅局限于此。
实施例所用原料和试剂均为市售产品。实施例中的“%”为质量百分比,特别说明的除外。
实施例中的收率均为摩尔收率。
实施例1:2-甲基-3,4-二氢-1(2H)-萘酮(Ⅲ)的制备
向接有搅拌、温度计、回流冷凝管、导气管的1000毫升四口烧瓶中,加入400克苯,60.0克(0.6摩尔)α-甲基-γ-丁内酯,于40-50℃范围内分10批加入300克(2.25摩尔)无水三氯化铝(每批加入30克),2小时加入完毕,此后80-82℃回流搅拌反应15小时,冷却至20-25℃,加入到250毫升35wt%浓盐酸和1500克冰水的混合物中,分层,水层用二氯甲烷萃取3次,每次200克,合并有机相,蒸馏回收二氯甲烷和苯,减压蒸馏(115-125℃/1mm汞柱)得到89.8克2-甲基-3,4-二氢-1(2H)-萘酮(Ⅲ),收率93.5%,气相纯度99.8%。
实施例2:2-甲基-3,4-二氢-1(2H)-萘酮(Ⅲ)的制备
向接有搅拌、温度计、回流冷凝管、导气管和恒压滴液漏斗的1000毫升四口烧瓶中,加入400克苯,60.0克(0.6摩尔)α-甲基-γ-丁内酯,于50-55℃范围内滴加427.0克(2.25摩尔)无水四氯化钛,2小时加入完毕,此后80-82℃回流搅拌反应15小时,冷却至20-25℃,加入到250毫升35wt%浓盐酸和1500克冰水的混合物中,分层,水层用二氯甲烷萃取3次,每次200克,合并有机相,蒸馏回收二氯甲烷和苯,减压蒸馏(115-125℃/1mm汞柱)得到88.9克2-甲基-3,4-二氢-1(2H)-萘酮(Ⅲ),收率92.6%,气相纯度99.9%。
实施例3:2-甲基-1-萘酚(Ⅳ)的制备
向接有搅拌、温度计、回流冷凝管、导气管和30wt%氢氧化钠水溶液吸收装置的500毫升四口烧瓶中,加入300克1,2-二氯乙烷,80.0克(0.5摩尔)实施例1方法所得2-甲基-3,4-二氢-1(2H)-萘酮(Ⅲ),加热,保持40-45℃之间,慢慢通入39.0克(0.55摩尔)氯气,约2-3小时通入完毕,此后45-50℃搅拌反应3小时,冷却至20-25℃,加入60.0克(0.6摩尔)40wt%氢氧化钠水溶液,30-35℃搅拌反应2小时,冷却至20-25℃,30wt%盐酸酸化体系pH值为3.0-4.0,分层,水层用1,2-二氯乙烷萃取3次,每次50克,合并有机相,蒸馏回收溶剂,干燥,得到77.1克2-甲基-1-萘酚(Ⅳ),收率97.6%,气相纯度99.9%。
实施例4:2-甲基-1-萘酚(Ⅳ)的制备
向接有搅拌、温度计、回流冷凝管、导气管和30wt%氢氧化钠水溶液吸收装置的500毫升四口烧瓶中,加入300克1,2-二氯乙烷,80.0克(0.5摩尔)实施例2方法所得2-甲基-3,4-二氢-1(2H)-萘酮(Ⅲ),62.5克(0.6摩尔)35wt%盐酸,保持35-40℃之间滴加61.5(0.55摩尔)30wt%双氧水,约3-4小时滴加完毕,此后40-45℃搅拌反应4小时,冷却至20-25℃,加入60.0克(0.6摩尔)40wt%氢氧化钠水溶液,30-35℃搅拌反应2小时,冷却至20-25℃,30wt%盐酸酸化体系pH值为3.0-4.0,分层,水层用1,2-二氯乙烷萃取3次,每次50克,合并有机相,蒸馏回收溶剂,干燥,得到75.9克2-甲基-1-萘酚(Ⅳ),收率96.1%,气相纯度99.7%。
实施例5:2-甲基-1-萘酚(Ⅳ)的制备
向接有搅拌、温度计、回流冷凝管、导气管和30wt%氢氧化钠水溶液吸收装置的500毫升四口烧瓶中,加入300克二氯甲烷,80.0克(0.5摩尔)实施例1方法所得2-甲基-3,4-二氢-1(2H)-萘酮(Ⅲ),111克(0.55摩尔)40wt%氢溴酸,保持25-30℃之间滴加56.0(0.5摩尔)30wt%双氧水,约3-4小时滴加完毕,此后25-30℃搅拌反应2小时,加入60.0克(0.6摩尔)40wt%氢氧化钠水溶液,25-30℃搅拌反应2小时,30wt%盐酸酸化体系pH值为3.0-4.0,分层,水层用二氯甲烷萃取3次,每次50克,合并有机相,蒸馏回收溶剂,干燥,得到78.1克2-甲基-1-萘酚(Ⅳ),收率98.8%,气相纯度99.9%。
实施例6:2-甲基-1,4-萘醌(Ⅴ)的制备
向接有搅拌的500毫升四口烧瓶中,加入31.6克(0.2摩尔)实施例3方法所得2-甲基-1-萘酚(Ⅳ),180克甲苯,搅拌溶解后,升温至80℃,持续通入干燥的空气,反应5小时,蒸干,残余物加0.5克活性炭,80克异丙醇,70-80℃搅拌脱色半小时,趁热过滤,滤液重结晶,过滤,干燥,得33.2克2-甲基-1,4-萘醌(Ⅴ),收率96.5%,液相纯度99.8%。
实施例7:2-甲基-1,4-萘醌(Ⅴ)的制备
向接有搅拌的500毫升四口烧瓶中,加入31.6克(0.2摩尔)实施例5方法所得2-甲基-1-萘酚(Ⅳ),180克异丙醇,搅拌溶解后,升温至90℃,持续通入干燥的空气,反应5小时,50-60℃下减压蒸馏回收100克异丙醇,加0.5克活性炭,70-80℃搅拌脱色半小时,趁热过滤,滤液重结晶,过滤,干燥,得33.9克2-甲基-1,4-萘醌(Ⅴ),收率98.6%,液相纯度99.9%。
实施例8:亚硫酸氢钠甲萘醌(Ⅰ)的制备
向接有搅拌、温度计的500毫升四口烧瓶中,加入100克无水乙醇,120克20wt%亚硫酸氢钠水溶液和34.4克(0.2摩尔)实施例7方法所得2-甲基-1,4-萘醌(Ⅴ),升温,温度保持40-45℃之间,反应4小时,降温至0℃,结晶2小时,过滤,得64.5克亚硫酸氢钠甲萘醌,收率97.5%,液相纯度99.8%。
所得产物的核磁数据如下:
1H NMR(400MHz,CDCl3)δ:1.82(s,3H),3.26(s,2H),7.51-7.99(m,4H)。
实施例9:亚硫酸氢钠甲萘醌(Ⅰ)的制备
向接有搅拌、温度计的500毫升四口烧瓶中,加入100克乙腈,120克20wt%亚硫酸氢钠水溶液和34.4克(0.2摩尔)实施例6方法所得2-甲基-1,4-萘醌(Ⅴ),升温,温度保持35-40℃之间,反应5小时,降温至0℃,结晶2小时,过滤,得63.9克亚硫酸氢钠甲萘醌,收率96.6%,液相纯度99.9%。
对比例:2-甲基-1,4-萘醌(Ⅴ)的制备
向接有搅拌、温度计的500毫升四口烧瓶中,加入15.8克2-甲基-1-萘酚,200克冰醋酸,25-30℃下,于1小时内滴加45.0克50wt%铬酐水溶液,滴加完毕后,25-30℃反应1小时,然后50℃反应30分钟,80℃反应15分钟,降温至室温,加入300克水,搅拌下使得物料析出,过滤,用清水洗涤至洗涤水pH中性,干燥后称量9.4克,收率54.7%,采用高效液相色谱检测,纯度为97.0%。
对比例表明:在该反应过程中收率较低,且使用铬离子氧化液作为氧化剂,反应的选择性差、后处理复杂,每生产一吨产品,产生60吨以上含铬酸性废水,环保性差。
Claims (1)
1.一种亚硫酸氢钠甲萘醌的制备方法,包括步骤:
(1)向接有搅拌、温度计、回流冷凝管、导气管的1000毫升四口烧瓶中,加入400克苯,60.0克α-甲基-γ-丁内酯(II),于40-50℃范围内分10批加入300克无水三氯化铝,每批加入30克,2小时加入完毕,此后80-82℃回流搅拌反应15小时,冷却至20-25℃,加入到250毫升35wt%浓盐酸和1500克冰水的混合物中,分层,水层用二氯甲烷萃取3次,每次200克,合并有机相,蒸馏回收二氯甲烷和苯,减压蒸馏,115-125℃/1mm汞柱,得到2-甲基-3,4-二氢-1(2H)-萘酮(Ⅲ);
或者,
向接有搅拌、温度计、回流冷凝管、导气管和恒压滴液漏斗的1000毫升四口烧瓶中,加入400克苯,60.0克α-甲基-γ-丁内酯(II),于50-55℃范围内滴加427.0克无水四氯化钛,2小时加入完毕,此后80-82℃回流搅拌反应15小时,冷却至20-25℃,加入到250毫升35wt%浓盐酸和1500克冰水的混合物中,分层,水层用二氯甲烷萃取3次,每次200克,合并有机相,蒸馏回收二氯甲烷和苯,减压蒸馏,115-125℃/1mm汞柱,得到2-甲基-3,4-二氢-1(2H)-萘酮(Ⅲ);
(2)向接有搅拌、温度计、回流冷凝管、导气管和30wt%氢氧化钠水溶液吸收装置的500毫升四口烧瓶中,加入300克1,2-二氯乙烷,80.0克2-甲基-3,4-二氢-1(2H)-萘酮(Ⅲ),加热,保持40-45℃之间,慢慢通入39.0克氯气,2-3小时通入完毕,此后45-50℃搅拌反应3小时,冷却至20-25℃,加入60.0克40wt%氢氧化钠水溶液,30-35℃搅拌反应2小时,冷却至20-25℃,30wt%盐酸酸化体系pH值为3.0-4.0,分层,水层用1,2-二氯乙烷萃取3次,每次50克,合并有机相,蒸馏回收溶剂,干燥,得到2-甲基-1-萘酚(Ⅳ);
或者,
向接有搅拌、温度计、回流冷凝管、导气管和30wt%氢氧化钠水溶液吸收装置的500毫升四口烧瓶中,加入300克1,2-二氯乙烷,80.0克2-甲基-3,4-二氢-1(2H)-萘酮(Ⅲ),62.5克35wt%盐酸,保持35-40℃之间滴加61.5g 30wt%双氧水,3-4小时滴加完毕,此后40-45℃搅拌反应4小时,冷却至20-25℃,加入60.0克40wt%氢氧化钠水溶液,30-35℃搅拌反应2小时,冷却至20-25℃,30wt%盐酸酸化体系pH值为3.0-4.0,分层,水层用1,2-二氯乙烷萃取3次,每次50克,合并有机相,蒸馏回收溶剂,干燥,得到2-甲基-1-萘酚(Ⅳ);
或者,
向接有搅拌、温度计、回流冷凝管、导气管和30wt%氢氧化钠水溶液吸收装置的500毫升四口烧瓶中,加入300克二氯甲烷,80.0克2-甲基-3,4-二氢-1(2H)-萘酮(Ⅲ),111克40wt%氢溴酸,保持25-30℃之间滴加56.0g 30wt%双氧水,3-4小时滴加完毕,此后25-30℃搅拌反应2小时,加入60.0克40wt%氢氧化钠水溶液,25-30℃搅拌反应2小时,30wt%盐酸酸化体系pH值为3.0-4.0,分层,水层用二氯甲烷萃取3次,每次50克,合并有机相,蒸馏回收溶剂,干燥,得到2-甲基-1-萘酚(Ⅳ);
(3)向接有搅拌的500毫升四口烧瓶中,加入31.6克2-甲基-1-萘酚(Ⅳ),180克甲苯,搅拌溶解后,升温至80℃,持续通入干燥的空气,反应5小时,蒸干,残余物加0.5克活性炭,80克异丙醇,70-80℃搅拌脱色半小时,趁热过滤,滤液重结晶,过滤,干燥,得2-甲基-1,4-萘醌(Ⅴ);
或者,
向接有搅拌的500毫升四口烧瓶中,加入31.6克2-甲基-1-萘酚(Ⅳ),180克异丙醇,搅拌溶解后,升温至90℃,持续通入干燥的空气,反应5小时,50-60℃下减压蒸馏回收100克异丙醇,加0.5克活性炭,70-80℃搅拌脱色半小时,趁热过滤,滤液重结晶,过滤,干燥,得2-甲基-1,4-萘醌(Ⅴ);
(4)向接有搅拌、温度计的500毫升四口烧瓶中,加入100克无水乙醇,120克20wt%亚硫酸氢钠水溶液和34.4克2-甲基-1,4-萘醌(Ⅴ),升温,温度保持40-45℃之间,反应4小时,降温至0℃,结晶2小时,过滤,得亚硫酸氢钠甲萘醌;
或者,
向接有搅拌、温度计的500毫升四口烧瓶中,加入100克乙腈,120克20wt%亚硫酸氢钠水溶液和34.4克2-甲基-1,4-萘醌(Ⅴ),升温,温度保持35-40℃之间,反应5小时,降温至0℃,结晶2小时,过滤,得亚硫酸氢钠甲萘醌。
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